The purpose of this work is the determination of the energies required for the formation of non-covalent bonds between molecules and ions in solution. Knowledge of the energetic requirements of such non-covalent bonds, particularly those involving water and biologically significant molecules, is fundamental to understanding molecular interactions and the changes in conformations that are integral to them. This research involves determining the thermodynamic quantities deltaH(std)298, deltaS(std)298, and deltaG(std)298 using the approach of equilibrium ion-molecule reaction chemistry. Hydration thermodynamics values were calculated from equilibrium constants measured over a temperature range of 0-136 degrees C at water partial pressures in the ion source ranging between zero and 100 mtorr. Equilibrium ion intensity measurements were made for at least 4 hydration states, i.e., zero through 3 water molecules associated with a core ion, and include at least 60 combinations of water partial pressures and temperatures covering the ranges of experimental variables. Results have been obtained for three different classes of molecules. First, an exhaustive study of the equilibrium clustering of 1-3 waters around n-alkylammonium, CnH(2n+1)NH3+, and the di- and tri-methyl ammonium ions, has shown a pattern of behavior consistent with water clusters forming around the charged portion of the ion and being influenced by the nature of the attached hydrophobic groups. Detailed analysis of the entropy values derived from these measurements is consistent with detecting the entropy change associated with the formation of an internal hydrogen bond. Second, the concepts of water organizing around a charge site and the formation of internal hydrogen bonds detected by substantial entropy decreases have been explored further with the investigation of the hydration energetics of simple alkyl-diols: 1,2-(OH)2-propane , 1,3-(OH)2-propane, 1,3-(OH)2- butane and 1,4-(OH)2-butane. The stepwise addition of water to protonated 1,2-(OH)2-propane shows a trend of diminishing exothermicity for each addition. While we were unable to obtain a direct measurement for the addition of the first water, we were able to estimate an upper limit on the exothermicity for this process based on the water partial pressure and temperature. We conclude that this first hydration step is energetically very favorable. The decreasing trend in energetics seen for 1,2-(OH)2-propane was observed for the addition of the first two water molecules to 1,3-(OH)2-propane, but was not maintained for the addition of the third water molecule. The addition of the third water to the complex was determined to be energetically more favorable than the addition of the second, and in addition was found to have a substantial decrease in the entropy for the process. These two observations lead to our concluding that the 1,3-(OH)2-propane trihydrate is an energetically and entropically favorable state. On the other hand, both of the butane diols behave in a manner consistent with the 1,2-propane diol. Third, are very recent results from studies of the hydration of several amino acids. Results from the equilibrium clustering of water with the neutral amino acids, glycine, valine and leucine, show behavior that is quite similar to that observed with the alkylammonium ions for the first two water molecules. The addition of the third water however is associated with a decrease in both enthalpy and entropy, suggesting the formation of intramolecular hydrogen bonds as seen in the 1,3-propane diol. in On the other hand, the results obtained to date in studies of the basic amino acids, arginine and lysine, are quite different. That is, while one might expect the energetics of adding the first water to these molecules to be highly favorable, we have determined that it is less energetically favorable than the addition of the first water to the neutral amino acids. This suggests the presence of internal hydrogen bonding being present before any water clusters are formed.